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1.
Bioorg Chem ; 97: 103675, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32143018

RESUMO

(±)-Petchilactones A-C (1-3), three pairs of enantiomeric meroterpenoids respectively with a 6/6/5/5 or a 5/5/5/7/6 ring system were isolated from Ganoderma petchii. Their structures including absolute configurations were assigned by using spectroscopic, computational, and X-ray diffraction methods. Compounds 1 and 2 represent a new skeletal meroterpenoid. Biological evaluation found that (-)-1 and (-)-3 could induce umbilical cord mesenchymal stem cells into keratinocyte-like cells.

2.
J Agric Food Chem ; 68(12): 3729-3741, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32125836

RESUMO

To seek new protoporphyrinogen oxidase (PPO) inhibitors with better biological activity, a series of novel diphenyl ether derivatives containing tetrahydrophthalimide were designed based on the principle of substructure splicing and bioisomerization. PPO inhibition experiments exhibited that 6c is the most potential compound, with the half-maximal inhibitory concentration (IC50) value of 0.00667 mg/L, showing 7 times higher activity than Oxyfluorfen (IC50 = 0.0426 mg/L) against maize PPO and similar herbicidal activities to Oxyfluorfen in weeding experiments in greenhouses and field weeding experiments. In view of the inspected bioactivities, the structure-activity relationship (SAR) of this series of compounds was also discussed. Crop selection experiments demonstrate that compound 6c is safe for soybeans, maize, rice, peanuts, and cotton at a dose of 300 g ai/ha. Accumulation analysis experiments showed that the accumulation of 6c in some crops (soybeans, peanuts, and cotton) was significantly lower than Oxyfluorfen. Current work suggests that compound 6c may be developed as a new herbicide candidate in fields.

3.
Fitoterapia ; : 104560, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32199957

RESUMO

Five new terpenoids including one new abietane diterpenoid (1), one new aromadendrane diterpenoid (6), two new norsesquiterpenoids (8 and 9), and a new cembrane-derived diterpenoid (12), together with seven known compounds were isolated from Populus euphratica resins. The structures of these new compounds, including their absolute configurations, were characterized by spectroscopic and computational methods. All the compounds except 8 were test for their neuroprotective activities. The result revealed that compounds 1, 7, and 10-12 display neuroprotective activities in glutamate-induced SH-SY5Y cells in a concentration-dependent manner.

4.
Org Lett ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167308

RESUMO

(±)-Dispirocochlearoids A-C (1-3), meroterpenoids with a 6/6/5/6/6/6 ring system, were isolated from Ganoderma cochlear. 1-3 are selective COX-2 inhibitors with an IC50 value of (-)-2 at 386 nM. Site-directed mutagenesis identified His351 as a COX-2 active site. In vivo anti-inflammatory activities of (-)-2 were performed against acute lung injury in mice.

5.
Fitoterapia ; 142: 104534, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32145314

RESUMO

Seven new compounds including three pairs of enantiomeric xanthine analogues (1-3), a pair of enantiomeric hypoxanthine analogue (4), and three pairs of enantiomeric N-acetyldopamine dimers (6-8), together with a known one (5) were isolated from the insect Cyclopelta parva. Their structures including absolute configurations were assigned by using spectroscopic and computational methods. Chiral HPLC was used to separate racemic 1-8. Biological evaluation found that 6b and 7a are potent COX-2 inhibitory agents with IC50 values at 385.2 nM and 868.8 nM respectively.

6.
Cell Death Dis ; 11(2): 89, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015333

RESUMO

Abnormal expression of the E3 ubiquitin ligase A20 has been found in some malignant cancers, including hepatocellular carcinoma (HCC). Here, we discovered that A20 is an E3 ubiquitin ligase for phosphofructokinase, liver type (PFKL) in HCC A20 interacts with PFKL and promotes its degradation, therefore inhibiting glycolysis in HCC cell lines. Downregulation of A20 in HCC cells promotes proliferation, migration, and glycolysis, all of which can be inhibited by targeting PFKL with RNA interference. Importantly, A20 is downregulated in advanced HCC tissues and inversely correlated with PFKL expression. Thus, our findings establish A20 as a critical regulator of glycolysis and reveal a novel mechanism for A20 in tumor suppression and PFKL regulation. Given that an increased level of glycolysis is linked with HCC, this study also identifies potential therapeutic targets for HCC treatment.

7.
Opt Lett ; 45(5): 1120-1123, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108785

RESUMO

In this Letter, we present, to the best of our knowledge, a novel illumination modulation method for reflective and fluorescent separation by using only one spectral image. Specifically, we present an optical system using off-the-shelf devices to generate high frequency illumination, which is desirable in reflective-fluorescent separation tasks. In addition, we employ the total variation regularization scheme to account for spectral-spatial correlation, which makes our method robust to noise. Experiments on both simulated and real data verify the effectiveness and practicality of our method.

8.
EMBO Rep ; 21(3): e48692, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32072744

RESUMO

Dysregulation of lipid homeostasis is intimately associated with defects in insulin secretion, a key feature of type 2 diabetes. Here, we explore the role of the putative lipid transporter ABCA12 in regulating insulin secretion from ß-cells. Mice with ß-cell-specific deletion of Abca12 display impaired glucose-stimulated insulin secretion and eventual islet inflammation and ß-cell death. ABCA12's action in the pancreas is independent of changes in the abundance of two other cholesterol transporters, ABCA1 and ABCG1, or of changes in cellular cholesterol or ceramide content. Instead, loss of ABCA12 results in defects in the genesis and fusion of insulin secretory granules and increases in the abundance of lipid rafts at the cell membrane. These changes are associated with dysregulation of the small GTPase CDC42 and with decreased actin polymerisation. Our findings establish a new, pleiotropic role for ABCA12 in regulating pancreatic lipid homeostasis and insulin secretion.

9.
J Agric Food Chem ; 68(11): 3403-3414, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32101688

RESUMO

Herbicide safeners selectively protect crops from herbicide damage without reducing the herbicidal efficiency on target weed species. The title compounds were designed by the intermediate derivatization approach and fragment splicing to exploit novel potential safeners. A total of 31 novel diazabicyclo derivatives were synthesized by the microwave-assistant method using isoxazole-4-carbonyl chloride and diazabicyclo derivatives. All synthetic compounds were confirmed by infrared, 1H and 13C nuclear magnetic resonance, and high-resolution mass spectrometry. The bioassay results demonstrated that most of the title compounds could reduce the nicosulfuron phytotoxicity on maize. The glutathione S-transferase (GST) activity in vivo was assayed, and compound 4(S15) revealed an inspiring safener activity comparable to commercialized safeners isoxadifen-ethyl and BAS-145138. The molecular docking model exhibited that the competition at the active sites of target enzymes between compound 4(S15) and nicosulfuron was investigated with respect to herbicide detoxification. The current work not only provided a powerful supplement to the intermediate derivatization approach and fragment splicing in design pesticide bioactive molecules but also assisted safener development and optimization.

10.
Environ Int ; 137: 105508, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32007686

RESUMO

BACKGROUND/AIM: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies have been done elucidating the role of DNA methylation linking prenatal Se and child neurobehavior. We aimed to investigate the associations between placental Se concentration and epigenome-wide DNA methylation in two U.S. cohorts, and to assess the association between Se-related DNA methylation modifications and newborns' neurobehavior. METHODS: We measured placental Se concentrations in 343 newborns enrolled in the New Hampshire Birth Cohort Study and in 141 newborns in the Rhode Island Child Health Study. Genome-wide placental DNA methylation was measured by HumanMethylation450 BeadChip, and newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales (NNNS). We meta-analyzed the associations between placental Se concentration and DNA methylation in each cohort, adjusting for covariates. We also fit multiple linear regression and ordinal logistic regression for methylation and newborn NNNS summary scores. RESULTS: We identified five Se-related differentially methylated CpG sites. Among them was cg09674502 (GFI1), where selenium concentration was positively associated with methylation (ß-coefficient = 1.11, FDR-adjusted p-value = 0.045), and where we observed that a one percent methylation level increase was associated with a 15% reduced odds of higher muscle tone in the arms, legs and trunk of newborns, (OR [95% Confidence Interval, CI] = 0.85 [0.77, 0.95]). We also observed for each interquartile range (IQR) increase in selenium concentration in the placenta, there was 1.76 times greater odds of higher hypotonicity (OR [95% CI] = 1.76 [1.12, 2.82]). CONCLUSIONS: Placental selenium concentration was inversely associated with muscle tone of newborns, and hypermethylation of GFI1 could be a potential mechanism underlying this association.

11.
Brief Bioinform ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065211

RESUMO

The locations of the initiation of genomic DNA replication are defined as origins of replication sites (ORIs), which regulate the onset of DNA replication and play significant roles in the DNA replication process. The study of ORIs is essential for understanding the cell-division cycle and gene expression regulation. Accurate identification of ORIs will provide important clues for DNA replication research and drug development by developing computational methods. In this paper, the first integrated predictor named iORI-Euk was built to identify ORIs in multiple eukaryotes and multiple cell types. In the predictor, seven eukaryotic (Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana, Pichia pastoris, Schizosaccharomyces pombe and Kluyveromyces lactis) ORI data was collected from public database to construct benchmark datasets. Subsequently, three feature extraction strategies which are k-mer, binary encoding and combination of k-mer and binary were used to formulate DNA sequence samples. We also compared the different classification algorithms' performance. As a result, the best results were obtained by using support vector machine in 5-fold cross-validation test and independent dataset test. Based on the optimal model, an online web server called iORI-Euk (http://lin-group.cn/server/iORI-Euk/) was established for the novel ORI identification.

12.
Nat Prod Res ; : 1-8, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31960727

RESUMO

Choushenpilosulynes D-G (1-4): four new polyynes were isolated from the roots of Codonopsis pilosula (Campanulaceae) cultivated in Yunnan province, China. Their structures were identified by spectroscopic methods. Bioactive evaluation showed that choushenpilosulynes E (2) and F (3) demonstrated potent inhibitory effect on lipid formation induced by 100 µM oleic acid stimulation. In addition, choushenpilosulyne F (3) uncovered inhibitory activity against the expression of human 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and squalene monooxygenase (SQLE) gene transcript in HepG2 cells.

13.
Nanoscale ; 12(3): 1994-2001, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31912077

RESUMO

As a single-elemental system, tellurium can exist stably in the form of layers with an intriguing multivalence character, which constructs a new member of the 2D family. However, the growth and electronic structure of tellurium films are still far from known at present. Here, combined with molecular beam epitaxy, scanning tunneling microscopy/spectroscopy measurements and density functional theory calculations, we report the geometric and electronic structures of tellurium grown on NbSe2 from sub-monolayer to few-layer films. At the sub-monolayer coverage, we obtain two types of adatom-induced ordered superstructures that are strongly coupled with NbSe2. With the increase in coverage, the few-layer tellurium films adopt the α-phase form, showing internal strain-induced ripple patterns in the few-layers and bulk-like in thick layers with distinct edge geometries. The band gap of α-tellurium films decreases with the increase in thickness, which is associated with notable in-gap states. These observations, corroborated with DFT calculations, emphasize the important role of the NbSe2 substrate in modulating the structural and electronic properties of tellurium films. Moreover, the interaction between tellurium adatoms and tellurium films leads to √2 × âˆš2 surface reconstruction prior to a new monolayer, conforming to our theoretical calculations. Our work clarifies the kinetic growth of tellurium films on NbSe2 and reveals the tunability of electronic properties via substrate modulation or surface decoration.

14.
Biochim Biophys Acta Mol Cell Res ; 1867(4): 118647, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31926942

RESUMO

Cisplatin-based chemotherapies have long been considered as a standard chemotherapy in ovarian cancer. However, cisplatin resistance restricts beneficial therapy for patients with ovarian cancer. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, that is implicated in the post-translational modification of diverse proteins. In this work, we found that ISG15 was downregulated in cisplatin resistant tissues and cell lines of ovarian cancer. Functional studies demonstrated that overexpression of wild type (WT) ISG15, but not nonISGylatable (Mut) ISG15 increased cell responses to cisplatin in resistant ovarian cancer cells. Furthermore, we found that WT ISG15 decreased ABCC2 expression at the protein level. Importantly, overexpression of ABCC2 blocked sensitizing effect of ISG15 on cisplatin. In addition, we identified that hnRNPA2B1 was recruited to 5'UTR of ABCC2 mRNA and promoted its translation, which was blocked by ISG15. We further demonstrated that hnRNPA2B1 could be ISGylated, and ISGylation blocked its recruitment to ABCC2 mRNA, thereby suppressed translation of ABCC2. Altogether, our data support targeting ISG15 might be a potential therapeutic strategy for patients with cisplatin-resistant ovarian cancer.

15.
Plant Physiol Biochem ; 148: 80-89, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31951944

RESUMO

Secondary metabolites (SMs) of medicinal plants are the material basis of their clinically curative effects. They are also important indicators for evaluating the quality of medicinal materials. However, the synthesis and accumulation of SMs are very complex, which are affected by many factors including internal developmental genetic circuits (regulated gene, enzyme) and by external environment factors (light, temperature, water, salinity, etc.). Currently, lots of literatures focused on the effect of environmental factors on the synthesis and accumulation of SMs of medicinal plants, the effect of the developmental growth and genetic factors on the synthesis and accumulation of SMs still lack systematic classification and summary. Here, we have given the review base on our previous works on the morphological development of medicinal plants and their secondary metabolites, and systematically outlined the literature reports how different environmental factors affected the synthesis and accumulation of SMs. The results of our reviews can know how developmental and environmental factors qualitatively and quantitatively influence SMs of medicinal plants and how these can be integrated as tools to quality control, as well as on the improvement of clinical curative effects by altering their genomes, and/or growth conditions.

16.
Plant J ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31960511

RESUMO

ß-Glucosidases (BG) are present in many plant tissues. Among these, abscisic acid (ABA) ß-glucosidases are thought to take part in the adjustment of cellular ABA levels, however the role of ABA-BG in fruits is still unclear. In this study, through RNA-seq analysis of persimmon fruit, 10 full-length DkBG genes were isolated and were all found to be expressed. In particular, DkBG1 was highly expressed in persimmon fruits with a maximum expression 95 days after full bloom (DAFD). We verified that, in vitro, DkBG1 protein can hydrolyze ABA-glucose ester (ABA-GE) to release free ABA. Compared with wild-type, tomato plants that overexpressed DkBG1 significantly upregulated the expression of ABA receptor PYL3/7 genes and showed typical symptoms of ABA hypersensitivity in fruits. DkBG1 overexpression (DkBG1-OE) accelerated fruit ripening onset by 3-4 days by increasing ABA levels at the pre-breaker stage and induced early ethylene release compared with wild-type fruits. DkBG1-OE altered the expression of ripening regulator NON-RIPENING (NOR) and its target genes; this in turn altered fruit quality traits such as coloration. Our results demonstrated that DkBG1 plays an important role in fruit ripening and quality by adjusting ABA levels via hydrolysis of ABA-GE.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31995465

RESUMO

A pink-pigmented, Gram-negative, rod-shaped, obligate aerobic bacterial strain, MIMD6T, was isolated from biological soil crusts in PR China. Cells grew at 20-37 °C (optimum, 30 °C), at pH 6-8 (optimum, pH 7) and with 0-1 % (w/v) NaCl (optimum, 0 %). Strain MIMD6T could use methanol or formate as a sole carbon source to grow, and carried methanol dehydrogenase genes mxa F and xox F, supporting its methylotrophic metabolism. The respiratory quinone was ubiquinone Q-10, the major fatty acids were C18 : 1ω7c (87.3 %), and the major polar lipids were diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unknown aminolipid and one unidentified glycolipid. The results of phylogenetic analyses based on the sequences of the 16S rRNA gene, seven housekeeping genes (dna K, rec A, rim O, rpI K, rpm G, rps R and rpo B) and methanol dehydrogenase genes indicated that strain MIMD6T formed a phylogenetic linage with members of the genus Methylobacterium. Strain MIMD6T was most closely related to Methylobacterium isbiliense DSM 17168T and Methylobacterium nodulans LMG 21967T with 16S rRNA gene sequence similarities of 95.7 and 95.2 %, respectively. The genomic DNA G+C content calculated via draft genome sequencing was 73.0 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain MIMD6T and the type strains of other Methylobacterium species were 70.7-82.0 and 24.6-30.0 %, respectively. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, strain MIMD6T represents a novel species of the genus Methylobacterium, for which the name Methylobacterium crusticola sp. nov. is proposed. The type strain is MIMD6T (=KCTC 52305T=MCCC 1K01311T).

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117540, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31680040

RESUMO

A novel and highly selective fluorescent 1,8-naphthalimide-based probe, 3, was designed and synthesized for rapid Cu2+ detection in a CH3CN-H2O (3:1, v/v, pH = 7.4) solution by means of a distinct hydrolysis mechanism via its Cu2+-promoting feature. Upon treatment with Cu2+, the fluorescence response of probe 3 at 550 nm abruptly decreased, which was visible to the naked eye, and this response was accompanied by a clear change of the color of the solution; the color changed from the original yellow color to colorless. This color change occurred due to the Cu2+-promoted hydrolysis of 3, which yielded a fluorescence-quenched product. It is inspiring that probe 3 exhibited excellent sensitivity, a short response time and strong anti-interference recognition. Compared with the allowable amount of Cu2+ (∼20 µM) in drinking water, the detection limit of 3 for Cu2+ is calculated to be 9.15 nM, which is much lower than the amount defined by standards. The probe can be successfully applied for the determination of Cu2+ in real aqueous samples. Furthermore, probe 3 can be used as a fluorescent sensor to detect Cu2+ in biological environments, demonstrating its low toxicity to organisms and good cell permeability in live cell imaging.

19.
Mol Plant ; 13(2): 246-265, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31706031

RESUMO

Suppression mechanisms mediated by transcriptional repressors commonly exist in diverse phytohormone signaling pathways. In Arabidopsis thaliana, JASMONATE-ZIM DOMAIN (JAZ) proteins are transcriptional repressors that function as negative regulators of diverse JA responses. Novel Interactor of JAZ (NINJA) is an adaptor protein connecting JAZs with the co-repressor, TOPLESS (TPL), to mediate gene repression in JA-dependent root growth inhibition and defense pathways. However, whether NINJA or other adaptor proteins are employed in other JA-responsive biological processes remains to be elucidated. In the present study, we demonstrate that a previously uncharacterized protein, ECAP (EAR motif-Containing Adaptor Protein), directly interacts with JAZ6 and JAZ8 and enhances their transcriptional repression activities. We provide evidence that ECAP is a novel adaptor protein for JAZ6/8 recruitment of the transcriptional co-repressor, TOPLESS-RELATED 2 (TPR2), into a transcriptional repressor complex that represses the WD-repeat/bHLH/MYB complex, an important transcriptional activator in the JA-dependent anthocyanin biosynthesis pathway. Our findings, together with previous reports, reveal that specific adaptor proteins play a critical role in distinct JA responses by pairing different JAZs (which possess overlapping but also specific functions) with the general co-repressors, TPL and TPRs.

20.
Oncogene ; 39(3): 546-559, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31501523

RESUMO

TRIM family proteins are defined as E3 ubiquitin ligases because of their RING-finger domains. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, that is implicated in the posttranslational modification of diverse proteins. Both TRIM29 and ISG15 play both pro-tumoral and anti-tumoral functions in cancer cells derived from different histology. In the current study, we demonstrated that correlation expression of TRIM29 and ISG15 in pancreatic ductal adenocarcinomas (PDACs). The current study demonstrated that TRIM29 knockdown destabilized ISG15 protein via promoting its processing by calpain 3 (CAPN3). Importantly, the current study found that TRIM29 knockdown suppressed cancer stem cell-like features of PDACs, which can be rescued by ISG15 independent of its conjugation function. In addition, the current study demonstrated that extracellular free ISG15 played an important role in maintenance of cancer stem cell-like features of PDACs. Thereby, the current study displayed a novel mechanism by which TRIM29 modulates ISG15 stability via CAPN3-mediated processing, and subsequently extracellular ISG15 maintains the cancer stem cell-like features of PDAC via autocrine mode of action.

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